DESCRIPTION (Applicant's abstract): The long-term objectives of the Principal Investigator are to evaluate the neural mechanisms that regulate the cardiovascular system in humans. The goal of this project is to evaluate sympathetic reflex responses to thermal stress at rest and during exercise. One key hypothesis underlying this proposal is that increases in muscle temperature will augment the discharge of mechanically and chemically sensitive afferents (Type III and IV) in the skeletal muscle. The increase in activity of these muscle afferents will augment muscle sympathetic nerve activity (MSNA; microneurography) during exercise. In attempt to determine if elevated temperature has a preferential effect on either mechanically or chemically sensitive muscle afferents, exercise that produces varying degree of mechanical and metabolic stimuli will be used. It is hypothesized the augmented MSNA response with local heating will be independent of changes in forearm blood flow. We will test this hypothesis by performing forearm exercise under ischemic conditions. Finally, based upon recent animal studies, we speculate that central thermoreceptors will not contribute to increases in MSNA during whole-body thermal stress. To test this hypothesis, MSNA will be recorded during rest and exercise before and after an elevation of body core temperature elicited by increasing environmental temperature and relative humidity to augment body heat storage. These studies will be conducted while maintaining the same muscle temperature and forearm blood flow during exercise under both thermal conditions. It is believed that these studies will provide direct evidence that the magnitude of muscle sympathetic discharge during exercise in humans is in part mediated by the increase thermal activation of muscle afferents but not activation of central thermoreceptors.